Allogeneic bone marrow transplantation has been used successfully to treat severe aplastic anemia and immunodeficiency diseases and for attempted curative therapy of lymphohematopoietic malignancies. Several problems prevent the full realization of the therapeutic potential of this procedure: non-acceptance of grafts, toxicity from the preparative regimens, acute and chronic graft-versus-host disease and prolonged immunodeficiency. Cyclosporin A (CsA) has been shown in preliminary studies in our rat bone marrow transplantation model to be as immunosuppressive as cyclophosphamide, prevent graft-versus-host disease, establish rapid immunological tolerance and accelerate the repair of the post-transplant immune defect. We want to study the effect of Cyclosporin A in depth in the rat model, evaluating its use as a preparative agent for marrow transplantation, an immunosuppressive agent to prevent and abolish sensitization and a tolerogenic agent to prevent and treat graft-versus-host disease and establish rapid immunologic tolerance. Furthermore, we want to study in depth how fast the CsA treated animal becomes fully immunologically competent. An attempt will be made to identify the mechanism of action of CsA by in vivo methods and in vitro proliferation assays. Apart from the important immunologic data obtained from these studies the experiments are designed to study the drug in a preclinical animal model as a basis for using CsA clinically in human bone marrow transplantation.